Integrin V 3 acting as membrane receptor for thyroid hormones mediates angiogenesis in malignant T cells

CAYROL FLORENCIA; DIAZ FLAQUE MARIA CELESTE; FERNANDO THARU; YANG SHAO NING; STERLE HELENA ; BOLONTRADE MARCELA; AMOROS MARIANA; ISSE BLANCA; FARIAS RICARDO; AHN H; TIAN YF; TABBO F; SINGH A; INGHIRAMI GIORGIO; CERCHIETTI LEANDRO; CREMASCHI GRACIELA

BLOOD, THE JOURNAL OF THE AMERICAN SOCIETY OF HEMATOLOGY - PRINT

AMER SOC HEMATOLOGY

Lugar: Washington; Año: 2015 vol. 125 p. 841 - 851

0006-4971

The interaction of lymphoid tumor cells with components of the extracellular matrix via integrin αvβ3 allows tumor survival and growth. This integrin was demonstrated to be the membrane receptor for thyroid hormones (THs) in several tissues. We found that THs, acting as soluble integrin αvβ3 ligands, activated growth-related signaling pathways in T-cell lymphomas (TCLs). Specifically, TH-activated αvβ3 integrin signaling promoted TCL proliferation and angiogenesis, in part, via the upregulation of vascular endothelial growth factor (VEGF). Consequently, genetic or pharmacologic inhibition of integrin αvβ3 decreased VEGF production and induced TCL cell death in vitro and in human xenograft models. In sum, we show that integrin αvβ3 transduces prosurvival signals into TCL nuclei, suggesting a novel mechanism for the endocrine modulation of TCL pathophysiology. Targeting this mechanism could constitute an effective and potentially low-toxicity chemotherapy-free treatment of TCL patients.